Methadone remains the standard of care for pregnant women being treated for opioid dependence, while studies of the effects of buprenorphine and naltrexone on a developing fetus continue. Although methadone’s efficacy, particularly in lower doses, is similar to that of buprenorphine,45 its adverse effect profile is worse. Adverse effects include drug-drug interactions, the potential for respiratory depression (especially when combined with alcohol or sedatives), QTc prolongation (which requires monitoring by electrocardiogram), sedation, and weight gain, and should be considered before selecting methadone as a maintenance pharmacotherapy.30,37,46 And, because relapse rates within 12 months of tapering off methadone have been reported to exceed 80%,47 both the clinician and the patient need to consider the likelihood of long-term, even lifelong, maintenance before initiating treatment.
Behavioral interventions are a vital part of the picture
Studies evaluating the extent to which various types and amounts of counseling improve outcomes compared with pharmacotherapy alone have had conflicting results.24,48 Nonetheless, most clinicians consider counseling to be a critical component of treatment for opioid dependence and recommend, at a minimum, either individual or group counseling (various modalities have been shown to be effective) and regular attendance at a self-help group like Narcotics Anonymous. Contingency management, a type of therapy that uses prizes as incentives for desired behaviors; and family therapy, individual counseling, and community-based programs have all been found to improve outcomes.6,49
CASE You refer Sam to an addiction psychiatrist, who stabilizes him on 16 mg buprenorphine/naloxone daily as part of an outpatient treatment program. Sam is enrolled in a weekly buprenorphine stabilization group, where he gives a urine sample each week. He also begins seeing a social worker weekly for counseling and attends Narcotics Anonymous meetings 2 to 3 times a week. At a follow-up appointment with you 6 months later, he reports that he has been abstinent from oxycodone for 6 months, his sleep is improved, and he feels better about his chances of finding another job.
Your role in safeguarding the patient
With the rising prevalence of opioid overdose, patient education aimed at crisis prevention is crucial, as well. Warn patients of the risk of accidental overdose, often associated with relapse, stressing the importance of continuing treatment and taking their maintenance medication exactly as prescribed.
There are other steps you can take to safeguard patients—eg, providing naloxone rescue kits to patients and their families when appropriate. You can also institute diversion and overdose prevention measures for patients taking buprenorphine or methadone—providing a lock box for take-home medication, implementing treatment contracts, and using a designated pharmacy to dispense buprenorphine, for example.26,27,50
Regular monitoring, urine drug screens (see TABLE W1), and random pill counts, in which patients are typically given 24 hours to bring in their prescribed medication so it can be counted, can also help keep patients on track. Treatment for concurrent psychiatric disorders—depression, anxiety, and personality disorders are common among patients with opioid dependence—is likely to improve the outcome of treatment, as well.
Pharmacokinetics of common opioids: Time detectable in urine*
|Drug (half-life)||Time detectable in urine||Comment|
|Codeine (2.5-3 h)||48 h||Pharmacogenetic-dependent effects may affect detection|
Transdermal (17 h)
Submucosal (7 h)
|Not usually detected in urine (lack of metabolites)||Excretion of transdermal fentanyl can last days|
IR (2.3 h)
ER (18.6 h)
|2-4 d||Significant interpatient variability|
|Methadone (8-59 h)||3 d|
|Morphine (1.5-2 h)||48-72 h||90% eliminated within 24 h|
IR (3.2 h)
ER (4.5 h)
|Often not detected in urine||High-fat meals may increase serum concentrations of ER formulation|
Parent drug (6-12 h)
Metabolite (30-36 h)
|ER, extended release; IR, immediate release.|
*Previously appeared in: McBane S, Weige N. Is it time to drug test your chronic pain patient? J Fam Pract. 2010;59:628-633.
Sources: Clinical Pharmacology [online]. Tampa, FL: Gold Standard Inc; 2010. Available at: http://cp.gsm.com. Accessed March 5, 2010; Drug Facts and Comparisons [online]. 2010. Available at: http://www.factsandcomparisons.com/. Accessed March 5, 2010.
CORRESPONDENCE Kevin P. Hill, MD, MHS, McLean Hospital, 115 Mill Street, Belmont, MA 02478; [email protected]